Hereditary metabolic myopathy with paroxysmal myoglobinuria due to abnormal glycolysis

Larsson, Lars‐Erik; Linderholm, Håkan; Müller, R; Ringqvist, T; Sörnäs, Rune

doi:10.1136/jnnp.27.5.361

Cited by 75 publications

(49 citation statements)

References 37 publications

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“…The disease is characterized by life-long exercise intolerance in which trivial bouts of exercise can cause tachycardia and palpitations, dyspnea, muscle fatigue, and lactic acidosis (1)(2)(3). Many ISCU myopathy patients experience periods of muscle weakness, pain, and swelling associated with rhabdomyolysis and myoglobinuria followed by muscle regeneration and resolution of these symptoms (1,4). Previous skeletal muscle biopsy analyses revealed a distinctive pattern of biochemical and histological hallmarks in ISCU myopathy, including deficiency of several mitochondrial iron-sulfur (Fe-S) proteins as well as mitochondrial iron overload in affected myofibers (4 -7).…”

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confidence: 99%

Tissue Specificity of a Human Mitochondrial Disease

Crooks

Jeong

Tong

et al. 2012

Journal of Biological Chemistry

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Background: ISCU myopathy is a disease caused by muscle-specific deficiency of the Fe-S cluster scaffold protein ISCU. Results: MyoD expression enhanced ISCU mRNA mis-splicing, and oxidative stress exacerbated ISCU depletion in patient cells. Conclusion: ISCU protein deficiency in patients results from muscle-specific mis-splicing as well as oxidative stress. Significance: Oxidative stress negatively influences the mammalian Fe-S cluster assembly machinery by destabilization of ISCU.

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confidence: 99%

Tissue Specificity of a Human Mitochondrial Disease

Crooks

Jeong

Tong

et al. 2012

Journal of Biological Chemistry

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“…Regulation is achieved in part by reflexes that originate in working muscle and are activated by metabolites produced in response to muscle energy demands (8). In certain disorders of muscle energy metabolism, circulatory and ventilatory exercise responses are exaggerated apparently due to anomalous accumulations of regulatory metabolites during muscular work (9)(10)(11)(12)(13). Comparable physiologic data are lacking in skeletal muscle electron transport defects.…”

Section: Introductionmentioning

confidence: 99%

Exercise intolerance, lactic acidosis, and abnormal cardiopulmonary regulation in exercise associated with adult skeletal muscle cytochrome c oxidase deficiency.

Haller¹,

Lewis²,

Estabrook³

et al. 1989

J. Clin. Invest.

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A 27-yr-old woman with lifelong severe exercise intolerance manifested by muscle fatigue, lactic acidosis, and prominent symptoms of dyspnea and tachycardia induced by trivial exercise was found to have a skeletal muscle respiratory chain defect characterized by low levels of reducible cytochromes a + a3 and b in muscle mitochondria and marked deficiency of cytochrome c oxidase (complex IV) as assessed biochemically and immunologically. Investigation of the pathophysiology of the exercise response in the patient revealed low maximal oxygen uptake (1/3 that of normal sedentary women) in cycle exercise and impaired muscle oxygen extraction as indicated by profoundly low maximal systemic arteriovenous oxygen difference (5.8 ml/dl; controls = 15.4±1.4, mean±SD). The increases in cardiac output and ventilation during exercise, normally closely coupled to muscle metabolic rate, were markedly exaggerated (more than two-to threefold normal) relative to oxygen uptake and carbon dioxide production accounting for prominent tachycardia and dyspnea at low workloads. Symptoms in our patient are similar to those reported in other human skeletal muscle respiratory chain defects involving complexes I and III, and the exaggerated circulatory response resembles that seen during experimental inhibition of the mitochondrial respiratory chain. These results suggest that impaired oxidative phosphorylation in working muscle disrupts the normal regulation of cardiac output and ventilation relative to muscle metabolic rate in exercise.

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“…We have previously described a 22-yr-old Swedish man with succinate dehydrogenase deficiency, severe exercise intolerance, and muscle fatigability and weakness (1), an autosomal recessive disease first recognized in several families from northern Sweden, with multiple siblings affected (7,8). In a repeat muscle biopsy from this patient, we have now documented low activity of complex III in addition to complex II, markedly reduced levels of the mature Rieske Fe-S protein of complex III in mitochondria with elevated levels of its precursor in the cytosol, and decreased levels of several subunits of complex I.…”

Section: Introductionmentioning

confidence: 99%

“…The immunoblot of complex I is harder to interpret because of the complexity of this protein, with 39 different subunits, 7 of which are encoded in the mitochondrial genome (44,45). It also contains approximately eight Fe-S clusters associated with the 75-, 51-, 24-, and 23-kD proteins and possibly two additional subunits (45)(46)(47).…”

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confidence: 99%

Mitochondrial myopathy with succinate dehydrogenase and aconitase deficiency. Abnormalities of several iron-sulfur proteins.

Hall¹,

Henriksson²,

Lewis³

et al. 1993

J. Clin. Invest.

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Recently, we described a patient with severe exercise intolerance and episodic myoglobinuria, associated with marked impairment of succinate oxidation and deficient activity of succinate dehydrogenase and aconitase in muscle mitochondria ( 1 ). We now report additional enzymatic and immunological characterization of mitochondria. In addition to severe deficiency of complex II, manifested by reduction of succinate dehydrogenase and succinate:coenzyme Q oxidoreductase activities to 12 and 22% of normal, respectively, complex III activity was reduced to 37% and rhodanese to 48% of normal. Furthermore, although complex I activity was not measured, immunoblot analysis of complex I showed deficiency of the 39-, 24-, 13-, and 9-kD peptides with lesser reductions of the 51-and 18-kD peptides. Immunoblots of complex III showed markedly reduced levels of the mature Rieske protein in mitochondria and elevated levels of its precursor in the cytosol, suggesting deficient uptake into mitochondria. Immunoreactive aconitase was also low. These data, together with the previous documentation of low amounts of the 30-kD iron-sulfur protein and the 13.5-kD subunit of complex II, compared to near normal levels of the 70-kD protein suggest a more generalized abnormality of the synthesis, import, processing, or assembly of a group of proteins containing iron-sulfur clusters. (J. Clin. Invest. 1993. 92:2660-2666.) Key words: myoglobinuria -electron transport * nicotinamide adenine dinucleotide (reduced form) dehydrogenase * ubiquinol-cytochrome c reductase * thiosulfate sulfurtransferase

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Hereditary metabolic myopathy with paroxysmal myoglobinuria due to abnormal glycolysis

Cited by 75 publications

References 37 publications

Tissue Specificity of a Human Mitochondrial Disease

Tissue Specificity of a Human Mitochondrial Disease

Exercise intolerance, lactic acidosis, and abnormal cardiopulmonary regulation in exercise associated with adult skeletal muscle cytochrome c oxidase deficiency.

Mitochondrial myopathy with succinate dehydrogenase and aconitase deficiency. Abnormalities of several iron-sulfur proteins.

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